Abstract: OBJECTIVE To characterize the oral colon-targeting pH-sensitive hydrogel of hydrocortisone sodium succinate(HSS) prepared in the previous work and to explore its colon-targeting characteristic. METHODS The structure of colon-targeting hydrogel of HSS(HSS-GEL) was analyzed by differential scanning calorimetry(DSC). The swelling degree of HSS-GEL at different pH(pH 1.2, pH 6.8, pH 7.4) was investigated; then the drug release degree of HSS-GEL in different media at different times through in vitro release experiments in simulated gastrointestinal environment was investigated; finally, the colon targeting of HSS-GEL by measuring the residual amount of HSS in different parts of the digestive tract at different times after intragastric administration of HSS-GEL was evaluated; and the disintegration degree of the cecal bacteria to HSS-GEL by in vivo incubation experiment in rat cecum was investigated. RESULTS The DSC results showed that konjac glucomannan and xanthan gum were combined by hydrogen bonding to form a stable network structure, and the drug was wrapped in the inner cavity of the gel; the swelling test results showed that the swelling rate of HSS-GEL at pH 7.4 was 5 times higher than that at pH 1.2, and the swelling rate at pH 6.8 was between them, which indicated that HSS-GEL had pH sensitivity; gastrointestinal environment in vitro release test showed that the release amount of HSS-GEL in artificial gastric juice was 17.63%, the release amount in pH 6.8 artificial juice was 25.56%, the release amount in artificial colon fluid at pH 7.4 was 86.14%; intestinal drug residue test in rats showed that within 1 to 3 hours after administration, HSS-GEL detected a small amount of HSS in the stomach, small intestine and colon, 5 h after administration, the amount of HSS detected in colon was dramatically increased, 7 hours after administration, the HSS concentration in the colon content reached the maximum, which was almost equal to the sum of the gastric and small intestinal drug doses. The above gastrointestinal environment in vitro release test and intestinal drug residue test all showed that HSS-GEL had good colon targeting and biodegradability; the in vivo incubation test showed that after the inhibition of clindamycin, the drug release rate in the cecum was only 3.55%, while the release rate of the control group was 82.99%, indicating that the cecal bacteria contributed greatly to the disintegration of the HSS-GEL gel material. CONCLUSION The HSS-GEL prepared in laboratory has good pH-sensibility, colon-targeting characteristic and biocompatibility.